Hypoxia-inducible factors (HIFs) are transcription factors that respond to cellular changes in oxygen levels, and specifically, to a condition of low physiological oxygen levels known as hypoxia. Most, if not all, oxygen-consuming species express HIF-1, which is a heterodimeric transcriptional complex comprised of an alpha and a beta subunit. The related protein HIF-2α can also dimerize with HIF-1β. Heterodimers that contain HIF-1α or HIF-2α seem to have overlapping but distinct specificities, with regard to physiological inducers and target-gene activation. HIF-3α is a third related protein that may function primarily as an inhibitor of HIF-1α.
The HIF pathway mediates the effects of hypoxia. HIF-1 upregulates several genes, including glycolysis enzymes and vascular endothelial growth factor (VEGF). Hypoxia affects an organism in many ways, including inhibiting cellular differentiation, promoting formation of blood vessels, promoting the formation of the vascular system in embryos, and promoting the migration of karatinocytes and the restoration of the epithelium in wounds.